Genetic analyzer

ABSTRACT

A nucleic acid analysis apparatus capable of selecting an optimal analysis method for every user and improving throughput is provided. In a genetic analyzer for measuring and analyzing amplification reaction of a nucleic acid in real time, an amplification curve is analyzed and a user can select conditions for terminating the amplification reaction upon detection of amplification. Further, a user can select conditions for selecting next processing after termination of the amplification reaction. A user can select, in situ, conditions for terminating the amplification reaction and conditions for selecting next processing upon detection of amplification and after the termination of amplification reaction. Alternatively, conditions for terminating the amplification reaction and conditions for selecting the next processing are registered previously and processing is performed automatically upon detection of amplification and after termination of the amplification reaction.

TECHNICAL FIELD

The present invention relates to a genetic analyzer of amplifying andinspecting a target nucleic acid.

BACKGROUND ART

As a method of inspecting infectious diseases or genes, a nucleic aidamplification technique of amplifying and detecting nucleic acids hasbeen utilized. An example of the amplification technique is a PCR(Polymerase Chain Reaction) method. The PCR method is a method ofrepeating temperature change (temperature cycle) to reaction solutionscontaining target nucleic acids to selectively amplify specific basesequences.

As a method of detecting an amplification reaction by the PCR method inreal time for analyzing a target nucleic acid quantitatively, there is areal time PCR method. In the existent real time PCR apparatus, identicaltemperature cycle is started to perform amplification reaction for aplurality of reaction solutions simultaneously.

In the existent nucleic acid inspection, the ratio of the step ofmeasuring the amplification reaction of a nucleic acid in which realtime PCR and fluorescence measurement are repeated in the analysisperiod is higher than that for the sample preparation step to result ina significant effect on the analytical processing speed.

Then, there is also a real time PCR apparatus of a configuration inwhich the detection of amplification is judged before a predeterminedamplification completion time and a reaction solution after terminationof the amplification reaction (after detection of amplification) isdischarged from a region to perform the amplification reaction andsupplies a fresh reaction solution is supplied to the region to performthe amplification reaction.

Further, in recent years, there has been known a method of analyzing agenetic polymorphism such as SNPs or mutation by using a reactionsolution after the PCR amplification reaction which is referred to asMelting analysis or HRM analysis (High Resolution Melting Analysis).

CITATION LIST Patent Literature

-   Patent Literature 1: Japanese Unexamined Patent Application    Publication No. 2009-106222

SUMMARY OF INVENTION Technical Problem

In the method described in the Patent Literature 1, detection ofamplification is judged by detection of a plateau. However, as a methodof detecting amplification, means capable of judging amplification at anearlier stage than the detection of the plateau such as detection of Ctvalue also exists. Accordingly, while there are a plurality ofconditions for judging the amplification, if the judgment for theinspection of amplification is defined uniformly, there was a problemthat a user cannot select an optimal condition for the termination ofamplification depending on a sample to be measured.

On the other hand, processing after the amplification reaction has alsobecome varied including, for example, HRM analysis. In the existentapparatus, Melting analysis or HRM analysis has been performed uniformlyafter lapse of a predetermined measurement completion time. However,since the Melting analysis or HRM analysis is not necessary for thereaction solution in which the amplification could not be inspected tocause loss in the analysis. Further, depending on the sample to bemeasured, Melting analysis or HRM analysis is sometimes unnecessary.Accordingly, there has been an increasing demand for a nucleic acidanalyzing apparatus capable of changing the processing after theamplification reaction in accordance with the result of theamplification reaction or the necessity of a user.

The present invention has been achieved in view of the foregoings and itintends to provide a genetic analyzer capable of selecting an optimalanalysis method depending on users and improving throughput.

Solution to Problem

For solving the problems described above, a nucleic acid analyzingapparatus of the invention is characterized in that reaction ofamplifying a nucleic acid is measured and analyzed in real time,detection of amplification is judged before a predetermined measurementcompletion time and a user can select conditions for terminating theamplification reaction when amplification is detected.

Since the user can select the conditions for terminating theamplification reaction after detection of amplification, throughput canbe improved in accordance with the measurement data required for theuser.

Further, the present invention is characterized in that a user canselect conditions for selecting the next processing after termination ofthe amplification reaction.

Since the user can select the next processing after the termination ofthe amplification reaction, throughput can be improved by performingonly the necessary next processing in accordance with the sample to bemeasured and analysis conditions.

Further, the invention is characterized in that the reaction foramplifying a nucleic acid is measured and analyzed in real time,detection of amplification is judged before a predetermined measurementcompletion time, and a user can select conditions for terminating theamplification reaction and conditions for selecting the next processingfor every result of amplification reaction when the amplification isdetected.

Since the user can select the conditions for terminating theamplification reaction after detection of amplification, the throughputcan be improved in accordance with the measured data necessary for theuser and, since the user can select the next processing in accordancewith the result of amplification, the throughput can be improved byperforming only the necessary next processing in accordance with asample to be measured, analysis conditions, and a necessary result.

Further, the genetic analyzer according to the invention ischaracterized by having an amplification detection mechanism providedwith holding units having a plurality of temperature control blocks eachholding at least one reaction vessel containing a reaction solution, anda temperature control device disposed to each of the plurality oftemperature control blocks and controlling the temperature of thereaction solution, thereby providing the processing of independentoperation for terminating the amplification reaction described above orthe next processing after termination of the amplification reactiondescribed above for each temperature control block.

By holding a plurality of temperature control blocks controlledindividually, processing operation individually optimal to samples to bemeasured and analysis conditions can be performed and throughput can beimproved.

Advantageous Effects of Invention

According to the nucleic acid analysis apparatus of the invention, sincethe conditions for terminating the amplification reaction can beselected, an operation for terminating the amplification reactionoptimal to a user can be performed and the throughput can be improved.

Further, since the conditions for selecting the next processing aftertermination of the amplification reaction can be selected, an analysisoperation optimal to a user can be performed.

Further, when the analysis method is previously selected and registeredin the apparatus, the apparatus can automatically perform an optimalanalysis operation and throughput can be improved.

Further, in an apparatus that holds a plurality of temperature controlblocks controlled individually, optimal processing operation can beperformed individually and the throughput can be improved.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is an entire schematic configurational view of a nucleic acidanalysis apparatus.

FIG. 2 is a block diagram showing a function of a control section of thenucleic acid analysis apparatus.

FIG. 3 is a graph showing an example of an amplification curve.

FIG. 4 is a graph showing a relation between a number of initial ofcopies a nucleic acid and an amplification curve.

FIG. 5 is a view illustrating a flow chart in the processing of a firstembodiment.

FIG. 6 is a view for explaining a screen for conditions of terminatingamplification reaction in the first embodiment.

FIG. 7 is a view for explaining a screen of selecting conditions ofdetecting amplification in the first embodiment.

FIG. 8 are views explaining a screen of selecting the next processing ina second embodiment.

FIG. 9 is a view for explaining a screen for selecting next processingfor every result of detection of amplification in a third embodiment.

FIG. 10 is a view for explaining setting of analysis condition on everyreaction vessel in the third embodiment.

FIG. 11 is a view for explaining a nucleic acid amplification device ina fourth embodiment.

DESCRIPTION OF EMBODIMENTS

One of best embodiments for practicing the invention is to be describedwith reference to the drawings.

FIG. 1 illustrates an entire configuration of a genetic analyzer 100 ofthe present invention. The genetic analyzer 100 is provided with aplurality of sample vessels 101 each accommodating a sample containing anucleic acid as a target for amplification processing, a sample vesselrack 102 accommodating the plurality of sample vessels 101, a pluralityof reagent vessels 103 accommodating various reagents to be added to thesamples, a reagent vessel rack 104 accommodating a plurality of thereagent vessels 103, reaction vessels 105 for mixing the sample and thereagent, a reaction vessel rack 106 accommodating a plurality of unusedreaction vessels 105, a reaction solution controlling position 107 foraccommodating the unused reaction vessels 105 for dispensing the sampleand the reagent from each of the sample vessels 101 and the reagentvessels 103 to the reaction vessels 105, a capping unit 108 for tightlyclosing the reaction vessels 105 containing the reaction solution as aliquid mixture of the sample and the reagent by a cap member (notillustrated), and a stirring unit 109 for stirring the reaction solutioncontained in the tightly closed reaction vessel 105.

Further, the genetic analyzer 100 is provided with a robot arm device112 having an X axis 110 of a robot arm disposed over the geneticanalyzer 100 so as to extend in the direction of the X axis (right andleft direction in FIG. 1) and a Y axis 111 of a robot arm disposed so asto extend in the direction of the Y axis (vertical direction in FIG. 1)and disposed movably to the X axis 110 of the robot arm in the directionof the X axis, a gripper unit 113 disposed movably to the Y axis 111 ofthe robot arm in the direction of the Y axis for gripping the reactionvessel 105 and transporting the vessel to each of the sections in thegenetic analyzer 100, a dispensing unit 114 disposed movably to the Yaxis 111 of the robot arm in the direction of the Y axis, sucking asample in the sample vessel 101 and a reagent in the reagent vessel 103and discharging (dispensing) them to the controlling reaction vessel 105disposed to the reaction solution conditioning position 107, nozzlechips 115 each attached to a portion of the dispensing unit 114 that isin contact with the sample or the reagent, a nozzle chip rack 116accommodating a plurality of unused nozzle chips 115, a nucleic acidamplification device 117 for conducting processing of nucleic acidamplification and detecting fluorescence to a reaction solutioncontained in the reaction vessel 105 in the course of amplification, anda discarding box 118 for discarding the nozzle chips 115 after use andthe reaction vessels 105 after use (after inspection), and a controlsection 121 having an input section 119 such as a keyboard and a mouseand a display unit 120 such as a liquid crystal monitor and controllingthe operation of the entire genetic analyzer 100 including the nucleicacid amplification device 117.

Each of the sample vessels 101 is administrated by identificationinformation such as a bar code for every contained sample andadministrated by position information such as a coordinate allocated toeach of the positions of the sample vessel rack 102. In the same manner,each of the reagent vessels 103 is administrated by identificationinformation such as a bar code for every contained reagent andadministrated by positional information such as a coordinate allocatedto each of the positions of the reagent vessel rack 104. Theidentification information and the positional information are previouslyregistered in the control section 121 and administrated. Further, eachof the reaction vessels 105 is also administrated in the same manner bythe identification information and the positional information.

The control section 121 includes at least an analysis planning sectionfor planning analysis operation in accordance with analysis conditionswhich are predetermined by the genetic analyzer and designated throughthe display section 120, an analysis performing section for controllingeach of the mechanisms in accordance with the analysis planning, and adata processing section for administrating fluorescence inspection data,etc. for every reaction vessel.

FIG. 2 illustrates a block diagram for a data processing section. Thedata processing section includes, at least, a fluorescence intensitycalculation section 200 for calculating the intensity of measuredfluorescence data, a temperature cycle administration section 201 foradministrating the temperature cycle for every temperature controlmechanism, a measurement time administration section 202 foradministrating the lapse of time in analysis, a measured dataadministration section 203 for administrating the data of thefluorescence intensity calculation section 200, the temperature cyclecontrol section 201, and the measurement time administration section 202for every measured sample, as well as an amplification curve analysissection 204, an amplification inspection judging section 205, and anamplification termination judging section 206. The amplification curveanalysis section 204 acquires an amplification curve from themeasurement data administration section 203 to calculate a Ct value anda plateau. The amplification detection judging section 205 judgesdetection of nucleic acid amplification for every amplification curve inaccordance with analysis conditions based on the calculated informationfor the Ct value and the plateau calculated by the amplification curveanalysis section 204. The amplification terminating judging section 206judges the termination of the amplification reaction based on theinformation on the calculation of the Ct value and the plateaucalculated by the amplification curve analysis section 204, informationon the temperature cycle, information on the amplification detectiontime, and the result of judgment for the detection of nucleic acidamplification of the amplification detection judging section 205. Theinformation of judging the amplification detection in the amplificationdetection judging section 205 and the information of judging thetermination of the amplification reaction in the amplification detectionjudging section 205 are transmitted to an analysis planning section (notillustrated) and analysis is replanned optionally.

FIG. 3 illustrates an example of measured data for amplificationreaction of a nucleic acid. Generally, the abscissa represents lapse oftime (or number of temperature cycles) and the ordinate representsfluorescence intensity.

An amplification curve 300 includes a lag phase 301, an exponentialphase 302, and a stationary phase 303. The lag phase 301 is sometimesalso referred to as a base line or a base line region. The stationaryphase 303 is sometimes referred to also as a plateau or a plateauregion.

Naturally, when the nucleic amplification reaction does not occur tillthe measurement completion time 308, there is a case where only the lagphase 301 is observed, or a case where the measurement completion time308 has been lapsed in the exponential phase 302 and the stationaryphase 303 is not observed.

The measurement completion time is identical with a temperature cyclecompletion timing after repeating temperature change (temperature cycle)by a predetermined number of times.

Such an amplification curve 300 includes a transition region 304 betweenthe lag phase 301 and the exponential phase 302. The transient region304 is also referred to as a cycle threshold value (Ct value) or anelbow value. Further, the amplification curve 300 includes a transitionregion 306 between the exponential phase 302 and the stationary phase303. The transition region 306 is a plateau detection point.Amplification of a nucleic acid can be judged by the Ct value detectiontime 305 and the plateau detection time 307.

Further, in the nucleic acid amplification curve, as the number ofinitial copies of the nucleic acid is larger upon startingamplification, the curve reaches the exponential phase and thestationary phase in a shorter time. Accordingly, when nucleic acidamplification curves are obtained by using standard samples dilutedstepwise, amplification curves 401 to 403 are obtained in the orderwhere the number of initial copies of the nucleic acid is larger asshown in FIG. 4. The number of initial copies of the nucleic acidcontained in an unknown sample can be identified by comparing the Ctvalue detection times 404 to 406 for detecting the Ct value 409 of theamplification curves 401 to 403 with the Ct value detection time 408 ofthe amplification curve 407 of the unknown sample. Naturally, the numberof initial copies of the nucleic acid can be identified also by usingthe plateau detection time in addition to the Ct value detection time404.

First Embodiment

As described above, the detection time for the Ct value or the plateauis extremely important in the analysis of the nucleic acid amplificationcurve. On the other hand, measured data on the stationary phase afterdetection of the Ct value or the plateau is sometimes unnecessarydepending on a user. In such a case, if the amplification reaction iscontinued till the measurement completion time, this lowers thethroughput of the entire genetic analyzer.

In view of the above, in this embodiment, presence or absence ofamplification is judged before a predetermined measurement completiontime and, when amplification is detected, conditions for terminating theamplification reaction is displayed on a screen, so that a user canselect conditions of terminating the amplification reaction.

FIG. 5 illustrates a process flow of this embodiment in the controlsection 121. In the flow, processing is preferably performed to all ofthe reaction vessels during amplification reaction for every measurementperiod for detection of fluorescence. Processing, for example, for everypredetermined cycle or processing for every cycle to a portion of thereaction vessels during amplification reaction is also possible.

In the flow, an amplification curve is at first acquired at step 500.For the amplification curve used herein, all of the fluorescence data upto the processing may be used, or only a portion of it may be used.Then, at step 501, it is judged whether conditions for terminating theamplification reaction have been selected or not. If it has not yet beenselected, the flow goes to step 502, and if it has already beenselected, the flow goes to step 505. At step 502, the amplificationcurve is analyzed and the detection of amplification is judged. At step503, when amplification is detected, the flow goes to a step 504 inaccordance with the result of judgment at step 502 and provides a screento a user for selecting conditions of terminating the amplificationreaction. In this screen, when the conditions for terminating theamplification reaction are selected, the conditions of terminating theamplification reaction is selected at step 501. Depending on theselected conditions, judgment for the detection of amplification may bechanged without selecting the conditions for terminating theamplification reaction. Further, the selected conditions for terminatingthe amplification reaction is used in the judgment for terminating theamplification at a step 505.

Then, at step 505, the amplification curve is analyzed and terminationof amplification is judged. At step 506, the flow goes to step 507 whenthe amplification is to be terminated in accordance with the result ofjudgment at step 505 and the amplification reaction of the reactionvessel is terminated.

FIG. 6(A) illustrates an example of display on a screen for selectingconditions for terminating the amplification reaction. The displayscreen displays conditions for terminating the amplification reaction,for example, that the amplification reaction is to be terminatedinstantly, the amplification reaction is continued till the completionof the measurement time and then terminated, or the amplificationreaction is continued for a desired time and then terminated, so that auser can select a desired terminating condition. Further, it ispreferably configured to have an input area 600 in the screen forinputting a desired time to continue the amplification reaction. Whilethe desired time is displayed on the unit of second in FIG. 6 (A), acondition equivalent to the time such as desired number of temperaturecycles, number of measurement, etc. may also be used as the condition.

Other examples of the condition for terminating the amplificationreaction include display of a selection screen again after lapse of thedesired time. Alternatively, the conditions for terminating theamplification reaction upon detection of the Ct value may also includesuch an option that the amplification reaction is terminated after thedetection of the plateau, or the screen for selecting the conditions forterminating the amplification reaction is displayed again after thedetection of the plateau.

As a more preferred embodiment, as shown in FIG. 6 (B), an amplificationdetection condition 601 or a sample ID 602 may be displayed. Inaddition, sample information, reagent information, etc. may be displayedor referred to so long as the information belongs to the relevantreaction vessel.

Further, as shown in FIG. 6(C), an amplification reaction curve 603 mayalso be displayed. Further, it is preferred that the amplificationreaction curve 603 can be displayed on an enlarged or reduced scale. Itis preferred that the maximum value on the abscissa of the amplificationreaction curve 603 is defined as a measurement completion time, so thata user can recognize the amplification curve and the remaining time upto the completion of measurement. Alternatively, a remaining time tillthe completion of measurement may be displayed directly. Suchinformation provides user a reference when selecting the conditions forterminating the amplification reaction.

For judging detection of amplification in the genetic analyzer,detection of amplification is judged by the detection of the Ct value orthe detection of the plateau. Alternatively, as shown in FIG. 7, it maybe configured such that the user can select the condition for detectingthe amplification based on the detection of the Ct value or thedetection of the plateau before starting the analysis. Further, the Ctvalue detection method maybe selected from the Crossing Point method orthe 2nd Derivative Maximum method and, in the case of the Crossing Pointmethod, a threshold value may be inputted.

Further, this genetic analyzer may be configured such that a user canregister the conditions for terminating the amplification reactionbefore starting analysis. That is, this nucleic acid analysis apparatuscan judge the presence or absence of amplification before apredetermined measurement completion time and, when the amplification isdetected, can terminate the amplification reaction automatically inaccordance with the conditions for terminating the amplificationreaction registered before starting analysis. Thus, the user can selectthe optimal condition for terminating the amplification reaction andunnecessary amplification detection time can be shortened to improvethroughput.

Further, the genetic analyzer may also be configured such that theconditions for terminating the amplification reaction can be set to thesample vessel, the reagent vessel, the reaction vessel, or a group ofthe reaction vessels collectively. Thus, the use can select the optimalcondition for completing the amplification in accordance with the sampleto be measured.

Second Embodiment

In this embodiment, when an amplification reaction is terminated,conditions for selecting the next processing are displayed on a screen,so that a user can select conditions of selecting the next processing.

FIG. 8 (A) illustrates an example of display on a screen of selectingconditions for next processing. The display screen displays conditionsfor selecting the next processing such that processing of Meltinganalysis or HRM analysis is performed, or thermal denaturationprocessing of deactivating an enzyme is performed, or a reaction vesselis discarded, so that a user can select desired next processing.

Other examples of conditions for selecting the next processing may alsooptionally include such combined conditions that a reaction vessel istransferred to a storage region, or subjected to thermal denaturationprocessing after the Melting analysis or HMR analysis, and it isdiscarded.

As a more preferred embodiment, as shown in FIG. 8 (B), an amplificationdetection condition 800 or a sample ID 801 may be displayed. Inaddition, sample information, reagent information, etc. may be displayedor can be referred to so long as the information belongs to a relevantreaction vessel.

Further, as shown in FIG. 8 (C), an amplification reaction curve 802 mayalso be displayed. Such information provides a reference to a user whenselecting the conditions for selecting the next processing.

Further, in this genetic analyzer, a user can also register theconditions for selecting the next processing before starting analysis.That is, this nucleic acid analysis apparatus can automatically transferto the next processing when the amplification reaction has beenterminated in accordance with the conditions for selecting the nextprocessing registered before starting analysis. Thus, only the nextprocessing selection condition required for a user can be selected andunnecessary processing can be excluded to improve throughput.

Further, in this genetic analyzer, the conditions for selecting the nextprocessing can be set to the sample vessel, the reagent vessel, thereaction vessel, or a group of the reaction vessels collectively. Thus,the user can select the optimal next processing in accordance with thesample to be measured.

Third Embodiment

In this embodiment, conditions for selecting next processing are heldfor every result of amplification reaction and the next processing isperformed automatically in accordance with the result of theamplification reaction. The result of amplification reaction preferablyincludes at least detection of the Ct value, detection of the plateau,and no detection of amplification and, in addition, may also displayinformation obtained by analyzing an amplification curve. It ispreferred that the items shown in the second embodiment can be selectedas conditions for selecting the next processing.

Further, as illustrated in FIG. 9, it is preferred that a user canregister conditions for selecting the next processing for every resultof the amplification reaction before starting amplification.

Further, in a more preferred embodiment, the conditions for terminatingthe amplification reaction are held, detection of amplification isjudged before a predetermined measurement completion time, and theamplification reaction is terminated in accordance with the conditionsfor terminating the amplification detection when the amplification isdetected. Further, it is preferred that a user can register theconditions for terminating the amplification reaction before startingthe amplification as shown in the first embodiment.

Further, in this genetic analyzer, conditions for detecting theamplification, conditions for terminating the amplification reaction,and conditions of selecting the next processing for every result ofamplification detection can be set to the sample vessel, the reagentvessel, the reaction vessel, or a group of the reaction vessels. Asshown in FIG. 10, ID for specifying the reaction vessel is displayed anobject 1000 for setting analysis conditions. Alternatively, the analysiscondition setting object 1000 may be configured so that the reactionvessel can be selected in view of a selection box in the form of a list,etc. and the analysis condition setting object may be changedsuccessively. Naturally, when the object 1000 for setting analysisconditions is changed, conditions of detecting the amplification,condition of amplification reaction, and conditions for selecting thenext processing for every result of detection of the amplification areupdated to the conditions of the object 1000 for setting analysisconditions being held. The sample vessel, the reaction vessel, or agroup of the reaction vessels can be designated to the object 1000 forsetting analysis conditions.

Thus, the user can select the optimal condition for terminating theamplification reaction and can select only the necessary next processingselection condition in accordance with a sample to be measured.Accordingly, analysis in which unnecessary amplification detection timeis shortened and unnecessary processing is eliminated can be achieved toimprove throughput in accordance with the necessity of the user.

Fourth Embodiment

In this embodiment, an embodiment of a nucleic acid amplificationapparatus for practicing the first to third embodiments is to bedescribed.

The nucleic acid amplification device illustrated in FIG. 11 has, on aholding unit base 1100, holding units 1102 provided with a plurality oftemperature control blocks 1101 holding reaction vessels, fluorescencedetectors 1103 for detecting fluorescence of a reaction solutioncontained in the reaction vessels, and a cover 1104 for covering theholding units 1102, and the fluorescent detectors 1103.

The temperature control block 1101 has a temperature control deviceincluding a Peltier element, a heat dissipation fin, and a temperaturesensor and has a function of controlling the reaction vessel held on theholding unit 1102 at a predetermined temperature. The temperature andthe timing for the change of temperature set in each of the temperaturecontrol blocks 1101 are controlled not depending on the temperature ofthe other temperature control blocks 1101.

The holding unit base 1100 has a rotatable structure although notillustrated. When the holding unit base 1100 rotates and the holdingunit 1102 passes over each of the fluorescent detectors 1103,fluorescence of the reaction solution contained in the reaction vesselis detected.

A relative speed between the reaction vessel and the fluorescentdetector 1103 can be controlled by controlling the rotational speed ofthe holding unit base 1100 to the fluorescent detector 1103 (relativerotational speed) upon measurement of fluorescence. The relative speedmay be at a constant speed, or fluorescence can be detected at aposition where the reaction vessel or the holding unit 1102 is opposedto the fluorescence detector 1103 while stopping them temporarily.

As described above, in the genetic analyzer having the nucleic acidamplification device provided with the temperature control device forevery reaction vessel, processing for terminating the amplificationreaction or next processing after the termination of the amplificationreaction described in the first to third embodiments is performed toindividual reaction vessels.

Further, the reaction vessel after termination of the amplificationreaction is carried out by the robot arm device 112 and the gripper unit113 from the nucleic acid amplification device and a new reaction vesselis carried into the nucleic acid amplification device. The new reactionvessel is newly provided with a temperature change (temperature cycle).By the provision of the temperature control device for every reactionvessel, analysis in the new reaction vessel can be started withoutdepending on the situation of analysis in other reaction vessels tofurther improve the throughput.

Further, it can also be configured to perform continuous processing forthe amplification processing, and processing of Melting analysis or HRManalysis, or thermal processing of deactivating an enzyme withoutmovement of the reaction vessel.

Further in FIG. 11, a plurality of holding units 1102 may also beprovided to the temperature control block 1101. In a case of a specificmeasurement vessel using an identical temperature reaction condition,throughput can be improved by continuous processing for Melting analysisor HRM analysis, or thermal processing after the termination of theamplification reaction for all the reaction vessels.

While the genetic analyzer of this invention has been described withreference to specific embodiments but the invention is not restricted tothem. Persons skilled in the art can provide various modifications andimprovements for the constitution and the function of the invention ineach of the embodiments and other embodiments within a range notdeparting from the gist of the invention.

LIST OF REFERENCE SIGNS

-   100 genetic analyzer-   101 sample vessel-   102 sample vessel rack-   103 reagent vessel-   104 reagent vessel rack-   105 reaction vessel-   106 reaction vessel rack-   107 reaction solution control position-   108 capping unit-   109 stirring unit-   110 X axis of robot arm-   111 Y axis of robot arm-   112 robot arm device-   113 gripper unit-   114 dispensing unit-   115 nozzle chip-   116 nozzle chip rack-   117 nucleic acid amplification device-   118 discarding box-   119 input section-   120 display section-   121 control section-   200 fluorescence intensity calculation section-   201 temperature cycle administration section-   202 measurement time administration section-   203 measured data administration section-   204 amplification curve analysis section-   205 amplification detection judging section-   206 amplification termination judging section-   300, 401 to 403, 407 amplification curve-   301 lag phase-   302 exponential phase-   303 stationary phase-   304 transition region between a lag phase and an exponential phase    (Ct value detection point)-   305, 404 to 406, 408 Ct value detection time-   306 transition region between an exponential phase and a stationary    phase (plateau detection point)-   307 plateau detection time-   308 measurement completion time-   409 Ct value-   500 to 507 steps in flow chart-   600 input area-   601, 800 amplification detection condition-   602, 801 sample ID-   603, 802 amplification reaction curve-   1000 amplification condition setting object-   1100 holding unit base-   1101 temperature control block-   1102 holding tool-   1103 fluorescence detector-   1104 cover

1. A genetic analyzer for measuring and analyzing an amplificationreaction of a nucleic acid in real time, in which detection ofamplification is judged before a predetermined measurement completiontime and, when amplification is detected, conditions for terminating theamplification reaction that the amplification reaction is to beterminated instantly, that measurement is continued till the measurementcompletion time and then terminated, and that an amplification reactionis continued for a desired time and then terminated are displayed on ascreen, and a user can select one of the conditions for terminating theamplification reaction.
 2. A genetic analyzer for measuring andanalyzing an amplification reaction of a nucleic acid in real time, inwhich a user can previously select one of conditions for terminating theamplification reaction that (a) detection of amplification is judgedbefore a predetermined measurement completion time and the amplificationreaction is instantly terminated when amplification is detected, (b)detection of amplification is judged before a predetermined measurementcompletion time and, when amplification is detected, measurement iscontinued till a measurement completion time and then terminated, or (c)detection of amplification is judged before a predetermined measurementcompletion time and, when amplification is detected, an amplificationreaction for a desired time is continued and then terminated, andprocessing for terminating the amplification reaction is performedautomatically in accordance with conditions for terminating theamplification reaction previously selected by the user.
 3. The geneticanalyzer according to claim 1, wherein the condition for detectingamplification in the judgment of detecting the amplification isdetection of a Ct value.
 4. The genetic analyzer according to claim 1,wherein the condition for detecting amplification in the judgment ofdetecting the amplification is detection of a plateau.
 5. The geneticanalyzer according to claim 1, wherein a user can previously select thatthe condition of detecting the amplification is detection of a Ct valueor detection of a plateau.
 6. The genetic analyzer according to claim 1,wherein a screen for conditions for terminating the amplificationreaction includes conditions for detecting amplification.
 7. The geneticanalyzer according to claim 1, wherein a screen for conditions forterminating the amplification reaction includes display of anamplification reaction curve.
 8. The genetic analyzer according to claim2, wherein the conditions for terminating the amplification reaction canbe set for every reaction vessel.
 9. A genetic analyzer for measuringand analyzing an amplification reaction of a nucleic acid in real time,in which conditions for selecting next processing are displayed on ascreen and, when the amplification reaction is terminated, a user canselect the conditions for selecting next processing.
 10. The geneticanalyzer according to claim 9, wherein a user can previously set theconditions for selecting the next processing and, when the amplificationreaction is terminated, the next processing is performed automaticallyin accordance with the conditions for selecting the next processing. 11.The genetic analyzer according to claim 9, wherein the screen for theconditions for selecting the next processing includes a result ofdetection of amplification reaction.
 12. The genetic analyzer accordingto claim 9, wherein the screen for the conditions for selecting the nextprocessing includes a display of an amplification curve.
 13. The geneticanalyzer according to claim 9, wherein the conditions for selecting thenext processing include processing of Melting analysis or HRM analysis.14. The genetic analyzer according to claim 9, wherein the conditionsfor selecting the next processing include a thermal treatment ofdeactivating an enzyme.
 15. The genetic analyzer according to claim 10,wherein the conditions for selecting the next processing can be set forevery reaction vessel. 16-26. (canceled)
 27. The genetic analyzeraccording to claim 1, including an amplification detection mechanismprovided with holding units having a plurality of temperature controlblocks each holding at least one reaction vessel containing a reactionsolution and temperature control devices disposed to each of thetemperature control blocks and controlling the temperature of thereaction solution.
 28. The genetic analyzer according to claim 27,wherein the holding unit has a mechanism of successively carrying in thereaction vessels.
 29. The genetic analyzer according to claim 27,wherein the holding unit has a mechanism of successively carrying outthe reaction vessels.
 30. The genetic analyzer according to claim 27,wherein the amplification reaction of the nucleic acid, processing of aMelting analysis or HRM analysis, or a thermal treatment of deactivatingan enzyme are performed continuously without moving the reaction vessel.